Chloroquine (CQ) remains the household drug for the treatment of malaria especially among pregnant women. However, there are reports that CQ inhibits the contractile process in non-pregnant rat's uterus. The aim of this study is to compare responses to CQ between non-pregnant and pregnant mice and identify some mechanisms involved. Experiments were carried out in non-pregnant and pregnant mice pretreated 24 hours before with 1.5 mg/kg-body weight stilboesterol given orally. Strips of uterine smooth muscle, approximately 5 mm in diameter, were mounted in a 20 ml organ bath containing De Jalon solution bubbled with a 95% O2-5% CO2 gas mixture. Responses of the strips to graded concentration of acetylcholine (ACh) (10(-9) to 10(-5) mol/L), oxytocin (OXY) (10(-5) to 10(-2) IU/ml) and CQ (10(-6) to 4 x 10(-4) mol/L) were investigated. The strips were then incubated in 4 x 10(-4) mol/L CQ for 15 mins and the cumulative dose responses for OXY were repeated. To investigate mechanism of action, the strips were incubated for 15 mins in N(w)-nitro L-arginine methyl ester (L-NAME) and the cumulative responses to CQ repeated. Each investigation was carried out in fresh tissue mounted on Grass Model FT03 force transducer coupled unto a 4-channel Grass Model 7D Polygraph. CQ (low to moderate level), ACh and OXY led to increases in contractile responses in the uteri. There were greater contractile responses in non-pregnant than pregnant mice to CQ and ACh. At high doses, CQ had an inhibitory effect on the uterine contraction. Incubating in CQ led to abolition of contractile responses to OXY and ACh. In the presence of L-NAME, inhibitory effect of CQ at high doses was attenuated in pregnant mice only. The results suggest that CQ at high doses inhibits contractile responses in non-pregnant and pregnant mice. Enhanced nitric oxide bioactivity attenuated this inhibitory effect.