Vitamin B12 and its binding proteins were measured in the serum and urine of four patients with Plasmodium falciparum who had renal insufficiency. The results showed that these patients had elevated serum transcobalamin II (TCII) levels which decreased to the normal level after recovery from azotaemia. There were direct relationships between serum TCII levels and blood urea-nitrogen or creatinine concentrations. The clearance and urinary excretion of vitamin B12 and TCII were significantly lower in the patients' group than in normal subjects. All these findings indicated that elevated serum TCII could occur in P. falciparum patients with renal insufficiency. This is probably caused by a reduction in renal plasma flow and glomerular filtration rate (GFR), secondary to a low or ineffective blood volume. The reduced GFR, in turn, reduces the TCII-B12 that filters through the glomeruli, resulting in decreased TCII-B12 uptake by the renal tubules, and thus slows down the TCII degradation by lysosomal enzymes. The decreased TCII catabolism therefore prolongs the TCII survival in the circulation and probably stimulates TCII synthesis and secretion in a feedback mechanism.