The function and sites of action of prostaglandins (PGs) vary in different animal species and tissues. In this study the influence of PGs (E1, E2, F2 alpha, D2) on muscle tone and nerve-mediated contraction was investigated in isolated bovine iris sphincter muscles. None of these PGs exogenously applied influenced the neuromuscular transmission. By contrast, after treatment with indomethacin, all PGs tested contracted the muscle much more than in the absence of indomethacin and under these conditions the PGs potentiated responses to cholinergic nerve stimulation. Their ED50 were (2.2 +/- 0.2) x 10(-7) M for PGE1, (6.7 +/- 0.3) x 10(-8) M for PGE2, and (7.3 +/- 0.4) x 10(-8) M for PGF2 alpha. PGE1 acted both on nerves and the muscle cell. PGE2 had its influence mostly via nerves. Whereas PGF2 alpha was less potent in the absence of indomethacin, PGF2 alpha had much more potent action primarily on nerves and partly on muscles after treatment with indomethacin. High concentrations of PGD2 had both pre- and post-junctional action with accompanying weak contraction of the muscle. Thus the degrees of pre- and post-junctional involvement were different from one another. There is a possibility that the application of these PGs alone masked the role of such endogenous agents. In order to understand and clarify the site and action of PGs, pretreatment with indomethacin may be useful in the iris muscle. In conclusion, PGs modulate cholinergic activity in the bovine iris sphincter muscles, as well as regulate the muscle tone.