Molecular size heterogeneities of PRL and GH in mice of the high mammary tumor C3H/St strain and low mammary tumor C57BL/St strain were compared under different physiological states. At least three size variants, the big (void volume), the intermediate (dimeric), and the little (monomeric) forms, of both hormones were detected in the sera and pituitary extracts. The big and the little forms of each hormone were the most prevalent; the intermediate form was detectable in only a few instances. In both strains, only big PRL was found in the sera of 15-day-old mice of both sexes. At 80 days of age, males of both strains still had only big PRL, but females of the low tumor C57BL/St strain now possessed only the little PRL, whereas those of the high tumor C3H/St strain continued to have mainly the big PRL. This pattern held true during late pregnancy. It is probable that this strain difference in the molecular size profile of PRL in adult females may be related to their incidence of mammary tumors. Lactation, nursing, perphenazine injection, estradiol benzoate treatment, all stimuli that enhance PRL secretion, increased the proportion of little PRL in sera and abolished the strain difference existing in the nonlactating state. Progesterone also increased the proportion of little PRL in female mice but not in males. Testosterone had no effect in either sex. Both the big and little forms of PRL were found in pituitary extracts, the big form comprising less than 5% in most animals except the 15-day-old mice, in which it constituted about 10% in both sexes. A small amount (approximately 2%) of intermediate PRL was also found when the pituitary extracts were chromatographed on a longer column. The pituitary patterns were not changed appreciably by any of the stimuli tested. These results suggest that little PRL may be the form that is predominantly secreted under most conditions. GH was present in the big and little forms in the sera of 15-day-old mice of both sexes, the little form being the major constituent. At 80 days of age, the pattern changed. Now the big GH was the greater constituent in mice of both sexes, with no appreciable difference between the two strains. During late pregnancy, serum GH levels increased to high levels in the C3H/St strain, yet most immunoreactive GH was present in the big form in mice of both strains. Lactation, nursing, or estradiol benzoate treatment produced no marked changes in the GH profile, but progesterone, testosterone, or perphenazine injections seemed to increase the proportion of the little GH in serum. Pituitary extracts from pregnant mice or others showed no demonstrable changes in the proportions of the different GH forms that correlated with the patterns found in serum. The results suggest that the larger forms of PRL and GH are natural entities in the mouse plasma, resulting mostly from postsecretional transformations in systemic circulatin...