Amniotic fluid from 16 diabetic and 78 healthy women at term was tested for capacity to cause mutations in Salmonella typhimurium bacterial tester strain TA98 (Ames test). Diabetes as well as heavy smoking increased the mutagenic activity of amniotic fluid. The difference between groups of diabetics and controls was significant in both nonsmokers and women who had smoked more than 5 cigarettes the last 48 h before delivery. It seems plausible that metabolic disturbances, perhaps enhanced by a lowered oxygenation, in some instances could produce mutagenic compounds. Mutagenic activity in amniotic fluid may be one of the factors underlying the increased incidence of congenital malformations in the offspring of diabetic women. Early mutations could cause such developmental errors in the embryos, and possibly also in future generations by damage to germ cells. Heavy smoking alone also caused an increase in mutagenic activity in term amniotic fluid. Our findings reflected an enhancing effect of smoking in diabetes. A pregnant diabetic woman who smoked would thus further endanger her already jeopardized pregnancy.