Although obese people have been reported to have a higher incidence of infections and some types of cancer, the immunocompetence of obese subjects remains poorly understood. To investigate whether obesity affects immunity, we studied obese subjects (BMI > 30 kg/m2) whose health was uncomplicated by any other disorder, including hyperglycemia. We compared mitogen-induced blastogenic response of peripheral blood lymphocytes in 34 obese subjects (mean +/- s.e. BMI: 38.4 +/- 2.0 kg/m2) and 35 non-obese controls (BMI: 21.3 +/- 0.4 kg/m2) who were matched for age and sex. The effects of weight reduction were also evaluated in 19 obese persons (BMI: 36.4 +/- 1.8 kg/m2) on a very low calorie diet. Mean (+/- s.e.) intracellular incorporation of [3H]-thymidine, on stimulation of T lymphocytes with either phytohaemagglutinin (PHA) or concanavalin A (Con A), and B lymphocytes with pokeweed mitogen, was significantly diminished in obese subjects compared to non-obese controls (47552 +/- 6917 vs. 83720 +/- 6252 cpm, P < 0.001; 30301 +/- 6018 vs. 45942 +/- 3723 cpm, P < 0.05; 13669 +/- 2971 vs. 23735 +/- 2048 cpm, P < 0.01, respectively). After weight reduction (BMI: 27.8 +/- 1.2 kg/m2), the mean T lymphocyte responses to PHA and Con A were increased significantly vs. baseline (98404 +/- 2444 vs. 50337 +/- 9516 cpm, P < 0.05 and 69523 +/- 15480 vs. 36695 +/- 8006 cpm, P < 0.05, respectively). Depressed blastogenesis of B lymphocytes was also augmented but was not statistically significant. The results suggest that obese subjects have underlying immune impairment in responsiveness of lymphocytes and that these impairments are reversible with adequate weight reduction.