Suspensions of luteal cells were prepared by collagenase dispersion of guinea-pig corpora lutea obtained at specific times during the oestrous cycle. Luteal cells incubated with hCG produced increased amounts of progesterone. For Days 3--13 of the oestrous cycle, the concentrations of hCG required for 50% of the maximum response were within the range, 1 x 10(-3) to 7 x 10(-3) i.u./ml, showing no marked loss of sensitivity to hCG with increasing luteal age. PGF-2 alpha (1 mumol/l), had no effect on basal production of progesterone but significantly inhibited hCG-stimulated progesterone production by luteal cells isolated on Days 7, 9, 10, 12 and 13 of the cycle. This concentration of PGF-2 alpha had no significant effect on progesterone production by luteal cells prepared earlier in the cycle (Days 3 and 5). It is concluded that (a) the luteolytic action of PGF-2 alpha in the guinea-pig is mediated, at least in part, by direct action on luteal cells, and (b) the cells from newly formed corpora lutea are resistant to the direct inhibitory action of PGF-2 alpha.