The model of delayed implantation produced by injection of progesterone (P4) following hypophysectomy on day 3 of pregnancy, was used to study the temporal relationship between phospholipase A2 (PLA2) activity and endogenous concentrations and/or in vitro production of prostaglandins (PGs) in the rat uterus during the early phase of implantation. No definitive correlation between the endogenous concentration of uterine PGs and their in vitro production, or PLA2 activity, was found following various treatments. However, an interesting interaction between various treatments and PLA2 activity, as well as PG production, was evident within 0.5 h-4 h. The unaltered PLA2 activity and PG production in the uterus at 0.5 h and 4 h after the last injection of P4 only suggest that PLA2 is probably the limiting step in PG synthesis in the P4 dominated uterus. On the other hand, the depressed uterine PG production at 0.5 h, in the face of unaltered PLA2 activity, in P4-primed rats injected with an optimal dose of estradiol-17 beta (E2: 20 ng/rat, i.v.) suggests a reduction in PG synthetase activity with estrogen. Because PLA2 activity remained unchanged, the stimulation in PGE, and to some extent PGF, production at 0.5 h following superimposition of histamine on the E2 treatment appears to be mediated via stimulation of PG synthetase. The increase in PGE and PGF production at 4 h as compared to 0.5 h following E2 injection was accompanied by increased PLA2 activity. However, PGF production did not exceed that obtained with only P4. Addition of histamine to the P4 and E2 treatment potentiated the stimulation of PG production at 4 h without further elevation in PLA2 activity. A suboptimal dose of E2 (10 ng/rat, i.v.) failed to increase PLA2 activity and PG production, compared to those obtained with 20 ng/rat of E2. However, coadministration of histamine with the low dose of E2 increased PG production to the level found with the optimal dose of E2; this was achieved without a significant change in PLA2 activity. On the other hand, histamine did not reverse the inhibitory effect of dexamethasone on E2 stimulation of PLA2 activity and PG production. Taken together these results suggest that histamine induced potentiation of PG production in P4 and E2 treated rats is probably mediated via activation of PG synthetase activity. PLA2 activity was increased significantly at 8 h after the last injection of P4. However, this increase in activity was reflected in increased PGE, but not PGF production.(ABSTRACT TRUNCATED AT 400 WORDS)