Thyroid hormones and leptin are both involved in the regulation of energy metabolism. Serum leptin concentrations were measured in women with thyrotoxicosis (n = 21, mean age 45 years) or hypothyroidism (n = 14, mean age 44 years) before and 3 months after restoration of the euthyroid state. Serum leptin concentration tended to increase in both hypothyroid (14.7 +/- 3.5 vs 17.8 +/- 3.9 ng/ml, p = 0.06) and thyrotoxic (11.9 +/- 1.7 vs 14.4 +/- 2.0, p = 0.08) women after treatment (values given as mean +/- SE in the untreated and the euthyroid state respectively). Body mass index (BMI) was lower in thyrotoxic women than in hypothyroid women in the untreated state (22.1 +/- 0.7 vs. 26.2 +/- 1.9, P < 0.05). BMI was not different between both groups after treatment (24.5 +/- 0.7 vs. 26.3 +/- 2.1, P = 0.37), due to an increase of BMI in the thyrotoxic women; BMI did not change in the hypothyroid group. After controlling for BMI in a multivariate regression analysis, serum leptin concentrations were lower in hypothyroid women than in thyrotoxic women (P < 0.05), whereas posttreatment values of leptin did not differ (p = 0.44). When leptin concentrations were expressed as standard deviation scores (Z-scores) from the mean value of female controls matched for BMI and age as reported earlier, Z-scores were lower in the hypothyroid than in the thyrotoxic women (-0.63 +/- 0.21 vs. 0.53 +/- 0.18, p = 0.001). After treatment, Z-scores did not deviate from the expected values (0.05 +/- 0.28 vs. 0.08 +/- 0.16, P = 0.98). Z-scores differed before and after treatment in both hypothyroid (P = 0.01) and thyrotoxic (P = 0.02) patients. In conclusion, these data obtained in thyrotoxic and hypothyroid women indicate that thyroid states modulates serum leptin concentrations independent of BMI, with a small decrease in hypothyroidism and a small increase in thyrotoxicosis.