The renal handling of human interferon-alpha has been evaluated by using an isolated and perfused rabbit kidney. IFN-alpha disappears from plasma with a t1/2 of 81 min and the fractional turnover rate is 0.84%/min. About 47 molecules of IFN-alpha are filtrated with 100 molecules of creatinine but most of the IFN is absorbed by tubular cells. This is the first report showing that human IFN-alpha is filtrated by the kidney, largely absorbed, most probably catabolized within tubular epithelium and excreted in negligible amounts with the urine.