Biochemical evidence of skeletal muscle damage is common in malaria, but rhabdomyolysis appears to be rare. To investigate the relationship between serum creatine kinase and myoglobin levels, muscle histology, and renal function in Plasmodium falciparum infections, we studied 13 patients with uncomplicated malaria, 13 with severe noncerebral malaria, and 10 with cerebral malaria. A muscle biopsy specimen was obtained from each patient for light microscopy and electron microscopy. Mean serum creatine kinase concentrations +/- SD were raised but similar for the three groups (258 +/- 277, 149 +/- 158, and 203 +/- 197 U/L, respectively; P = .5). The mean serum myoglobin level +/- SD was highest in cerebral malaria (457 +/- 246 vs. 170 +/- 150 and 209 +/- 125 ng/mL in uncomplicated and severe malaria, respectively; P < .01) and correlated with the mean serum creatinine level (r = .39 for 36 patients; P = .02). The number of intravascular parasites, proportion of mature forms, and glycogen depletion were highest in biopsy specimens from patients with cerebral malaria. Myonecrosis was not observed. Muscle appears to be an important site for P. falciparum sequestration, which could contribute to metabolic and renal complications.