This study compares the effects of two inhibitors of prostaglandin synthesis, indomethacin and aspirin, on the longitudinal muscle (LM) and circular muscle (CM) of the rat uterus. Microelectrode and tension records were obtained from LM and CM strips isolated from uteri of normal animals on gestation Days 17-21 and during delivery and on the drug-treated rats on Days 21-22. In normal pregnant rats the pattern of spontaneous uterine activity changes progressively throughout gestation. The changes are most prominent in the CM and consist of a gradual decline in membrane potential and alteration in the configuration of the action potential from a plateau-type, single spike (Day 17) to repetitive spikes synchronous with contraction (Day 21 and delivering). Although the frequency of contraction declines over this period, the contractions become longer and more regular and synchronize with spike trains as pregnancy progresses. Indomethacin and aspirin delayed parturition by at least 24 h and prevented the "evolution" of the electrical and mechanical activity in both LM and CM. The actions of these agents were different in the two muscle layers and were unique for each drug. While our results do not exclude the possibility that inhibition of prostaglandin synthesis is one component of the actions of indomethacin and aspirin, they also suggest that the drugs have additional effects of their own. The study also emphasizes differences in the activity of the LM and CM in the rat uterus not only during pregnancy but also with respect to the actions of various drugs.