To clarify a possible role for atrial natriuretic peptide in the pathophysiology of pregnancy complicated by hypertension, we studied plasma levels of atrial natriuretic peptide in 176 pregnant women with or without hypertension. Plasma atrial natriuretic peptide levels in normal pregnant women showed a gradual increase as pregnancy advanced, but the mean (+/- SD) concentrations in women in each trimester (34.8 +/- 14.7 pg/ml in the first trimester, n = 35; 38.7 +/- 12.2 pg/ml in the second trimester, n = 34; and 43.1 +/- 20.0 pg/ml in the third trimester, n = 71) did not differ statistically from the mean plasma atrial natriuretic peptide level in nonpregnant women (38.2 +/- 13.6 pg/ml, n = 44). In contrast, plasma atrial natriuretic peptide levels were elevated in 9 of the 12 women who had hypertension. The mean plasma atrial natriuretic peptide concentration in these patients (162 +/- 95.2 pg/ml) was significantly (p less than 0.01) higher than in normal pregnant women and in nonpregnant controls. On the other hand, 11 pregnant women with proteinuria or edema but without hypertension had normal plasma atrial natriuretic peptide levels. These results suggest that plasma atrial natriuretic peptide levels are normal in women during uncomplicated pregnancy, while the levels are elevated in pregnancy complicated by hypertension. Increased atrial natriuretic peptide secretion in the latter condition may reflect a mechanism of compensation that operates in response to water and sodium retention.