We have found previously great interindividual variations in the binding of digoxin to skeletal muscle even after standardized rest. The present study was performed in order to find out if there is a difference in the binding of digoxin to slow- and fast-twitch fibres in man at rest and after moderate exercise. Seven healthy digitalized subjects (digoxin 0.50 mg/day) were investigated after 90 min of supine rest and after a 1 h moderate bicycle exercise. Muscle biopsy specimens were taken immediately before and 5 min after exercise and dissected under a microscope to single fibres. After histochemical typing of all fibres the digoxin content in slow- and fast-twitch fibres was measured separately. At rest, digoxin binding to slow-twitch fibres was 33% higher than to fast-twitch fibres (P less than 0.01). During exercise the digoxin binding increased by 28% in slow-twitch fibres but was unchanged in fast-twitch fibres. The difference in digoxin binding to the two fibre types may explain, at least partly, the interindividual variations in the binding of digoxin to skeletal muscle.