Overhydration can contribute to fatal complications of falciparum malaria, even though renal function may be normal. In this context, the role of inappropriate secretion of antidiuretic hormone (ADH) has been controversial. Therefore, we have analyzed ADH serum concentrations together with serum osmolality and sodium levels in serum and urine of 17 consecutively studied patients with severe falciparum malaria. Serum sodium levels were low in 13 of 17 patients upon admission and returned to normal levels during antiparasitic therapy. Urine sodium levels were low in seven of 13 patients before treatment and increased during therapy. Urine sodium concentrations were high, however, in the remaining six patients. Serum osmolality was lower in these six patients than in the other seven hyponatremic patients (P < 0.002). In relation to serum osmolality, ADH levels were inappropriately high in these six patients, which confirms the presence of inappropriate secretion of ADH. Serum creatinine levels were not higher in these six patients than in those without inappropriate secretion of ADH. Inappropriate secretion of ADH seemed to be a major cause of hyponatremia, since other factors that could lead to this condition were not found in these six patients. In conclusion, we have shown, that human falciparum malaria can be associated with inappropriate secretion of ADH.