We studied the impact of Plasmodium falciparum on nutritional status in a longitudinal cohort of 147 young men in western Kenya, where malaria transmission is intense and perennial. All volunteers received treatment to eradicate parasitemia and then provided weekly blood smears during a 16-week transmission season. We measured body mass index (BMI), pubertal development, frequency and density of parasitemia, and tumor necrosis factor (TNF)-alpha production by peripheral blood mononuclear cells. During early puberty, mean parasite density had a strong negative effect on the natural increase in BMI. Among older individuals, TNF-alpha production in response to malarial antigen predicted a significantly lower BMI (P<.03), equal to 4.6 kg for a man of average height. Our data indicate that burden of parasitemia has a detrimental effect on the nutritional status of early adolescents and that malaria may continue to influence nutritional status among older adolescents and adults via host elaboration of proinflammatory cytokines. These effects of malaria may have pervasive health and socioeconomic consequences in areas where malaria is endemic.