In a previous study we have demonstrated that cervical stimulation (CS) induces alpha-MSH release. The present experiments were undertaken to (1) examine the pattern of serum alpha-MSH during CS-induced pseudopregnancy (PSP) and (2) assess the possibility that alpha-MSH contributes to the induction and maintenance of PSP. Throughout PSP serum alpha-MSH fluctuated in a cyclic manner demonstrating two daily surges which occurred between 12.00 and 13.00 h (diurnal surge) and between 24.00 and 04.00 h (nocturnal surge). Chronic exposure of animals to alpha-MSH administered via minipumps (24 micrograms/day, starting on the morning of estrus), induced PSP as determined by deciduoma formation and persistence of a characteristic diestrous vaginal cytology. Furthermore, insertion of an alpha-MSH-containing minipump at diestrus 1 (D1) resulted in progesterone and prolactin (PRL) levels on the afternoon of diestrus 2 (D2) similar to those levels found on day 2 of PSP. Uterine weight was significantly decreased in alpha-MSH-treated rats and pseudopregnant rats as compared with cyclic D2 controls. alpha-MSH was found to release PRL indirectly, through stimulation of adrenal progesterone. This effect, however, necessitates the presence of the ovaries as a source of estradiol (EB) since it is demonstrable in intact and acutely ovariectomized rats, but not in chronically ovariectomized animals. EB treatment of chronically ovariectomized rats is capable of restoring the sequence. These results indicate that, as demonstrated for PRL, cervical stimulation initiates rhythmic daily surges of alpha-MSH secretion which are maintained through PSP.(ABSTRACT TRUNCATED AT 250 WORDS)