Prolactin is associated with the development of mammary tumors in rats. The aim of the present study was to evaluate whether strain differences in susceptibility to the development of mammary tumors could be explained by genetic differences in the response of the pituitary to chronic stimulation by estrogens. Prolactin levels were measured in plasma from rats of the Sprague-Dawley, Wistar WAG/Rij and Brown Norway BN/BiRij strains before and at different times after subcutaneous implantation of estradiol-17 beta in cholesterol/paraffin pellets. In all strains plasma prolactin was elevated from the second week after implantation of the pellet, although there were quantitative differences between the responses. At 32 weeks after implantation of the pellets the plasma level of prolactin in Sprague-Dawley rats was 1247 +/- 367 ng NIAMDD prolactin RP-1/ml (mean +/- S.E.M), whereas Wistar WAG/Rij and Brown Norway BN/BiRij had plasma prolactin levels of 679 +/- 211 and 182 +/- 19 ng/ml respectively. Between 52 and 104 weeks after implantation these values rose to 4016 +/- 1116, 5004 +/- 1053 and 808 +/- 129 ng/ml respectively. The plasma concentration of prolactin of rats in this age group was strongly associated with the occurrence of pituitary adenomas in all three strains. In untreated rats, the concentration of prolactin in the plasma increased with age to only 200-400 ng/ml at 12-24 months of age but no significant differences were observed between the three rat strains. It is concluded that observed differences in spontaneous and estrogen-mediated mammary tumor development in these rat strains cannot be explained by genetic differences in the plasma concentration of prolactin.