Investigations were performed to explore changes in fetal toxicity induced by acetylsalicylic acid (ASA) in pregnant animals treated by various means for maternal alterations. The fetotoxicity induced by ASA (500 mg/kg s.c.) was higher in rats than in mice. In mice with low enzyme activity, those displaying a longer sleeping time in pentobarbital-induced sleep, the ASA-fetotoxicity was higher than that of mice with shorter sleeping time. In rats pretreated with phenobarbital (0.05%), Zn (10 mg/l) and Cu (10 mg/l) in tap water and cysteine (200 mg/kg s.c.), fetal toxicity of ASA was reduced, whereas it was enhanced in rats pretreated with SKF-525A (200 mg/kg s.c.) and alpha-naphthyl acetic acid (200 mg/kg p.o.) and in nephrectomized rats. The UDPGT activity in hepatic 9000 x g supernate was higher in mice than in rats and the activity of mice was increased by phenobarbital and Cu. This study indicates that ASA-induced fetotoxicity can be positively modified by alterations in drug metabolizing activity.