It has been suggested that tobacco smoking during pregnancy reduces birth weight by lowering production rates or levels of total pregnancy estrogens. To evaluate this hypothesis, we examined total estrogen levels by radioimmunoassay in the blood of 141 pregnant women attending the maternity clinic of a major university hospital in Athens during their 26th week of pregnancy. Forty-nine of these women were regular smokers before and during their pregnancy, whereas the remaining 92 had never been regular smokers and did not smoke at all during their pregnancy. Birth weight of offspring was lower among smokers than among nonsmokers by 190.8 g, with a 90% confidence interval of 41.1 to 340.5 g, and higher among women with higher serum estrogen levels (slope b = 1.2 g per 1000 pg/ml with a 90% CI of 0.2 to 2.2 g). There was, however, only a small negative relation between tobacco smoking and serum estrogen levels; in smokers, total estrogen levels were reduced to 91% of the corresponding levels among nonsmokers.