Reproductive history was obtained and the activity and electrophoretic pattern of the blood enzyme galactose-1-phosphate uridyl transferase (transferase) was measured in 104 adult Caucasian women, <70 years of age, sampled from the general population. Fifteen women were identified as carriers for the Duarte (Gt(D)) or galactosemia (gt) variants of transferase - genes associated with reduced transferase activity compared with normal (Gt+). The mean age at menopause for 8 women with a natural menopause who were Gt(D)/Gt+ or gt/Gt+ was 44.8, significantly younger (P = 0.007) than the mean age of 49.2 reported by 31 naturally postmenopausal subjects with Gt+/Gt+ genotypes and normal transferase activity. Compared with the latter group, women who were Duarte or galactosemia carriers were 13.7 times more likely to have a menopause before age 48 (with 95% confidence limits of 2.0 to 95.5). Six of 13 (46%) married women who were Gt(D)/Gt+ or gt/Gt+ reported more than 2 years' trying to achieve a pregnancy, compared with 11 of 74 (15%) with normal genotypes and activity (P = 0.02). The authors conclude that genetic deficiency of transferase may be associated with infertility and early menopause.