In this study we examined the stimulatory effects of PGF(2 alpha) on progesterone secretion by porcine luteal cells on different days of the estrous cycle, and the effects of PGF(2 alpha) A23187 and PMA on progesterone secretion by isolated large and small luteal cells, in vitro. Corpora lutea were obtained from cycling pigs (days 6-16), collagenase dispersed and luteal cells incubated in medium 199 in the absence or presence of increasing doses of PGF(2 alpha), A23187, and PMA. Progesterone concentrations in spent media were measured by RIA. PGF(2 alpha) stimulation of progesterone secretion by mixed luteal cells did not vary significantly throughout the estrous cycle. Progesterone secretion by large, but not small, luteal cells was increased (p<0.05) in a dose-dependent fashion by PGF(2 alpha) A23187 also caused a dose-dependent increase in progesterone secretion by large luteal cells but inhibited small luteal cells. Progesterone secretion by both large and small luteal cells was significantly increased by increasing doses of PMA. We conclude that the stimulatory response of luteal cells to PGF(2 alpha) in vitro did not correlate with PGF(2 alpha) receptor concentrations (not measured in this study), and we speculate that calcium/protein kinase C may be involved in mediating the stimulatory action of PGF(2 alpha) on luteal cell progesterone secretion.