Serum colchicine levels were determined by radioimmunoassay after a 1-mg bolus injected intravenously in 4 patients with familial Mediterranean fever and in 6 normal subjects. Mean elimination half-life (t1/2) (+/- SEM) was 157 +/- 20 min in the patients and 65 +/- 15 min in the normal subjects (p less than 0.005). Total clearance was 239 +/- 50 ml/min in the patients and 601 +/- 155 ml/min in the normal subjects (p less than 0.05). Volume of distribution (Vdarea) was 76 +/- 16 and 49 +/- 91 and did not differ significantly. In 8 patients receiving colchicine prophylactically with good clinical response, serum colchicine ranged from 0.3 to 2.4 ng/ml after daily doses of 1 mg orally. In 2 responding patients 2-mg doses orally induced levels from 4 to 10 ng/ml, and in one (a nonresponder) a 3-mg dose induced levels of 7.5 to 13 ng/ml. Of 3 patients receiving 2 mg daily with unsatisfactory clinical responses, serum levels were not detectable in one and in the low range of 1.5 to 5.4 ng/ml in the others. It is suggested that lack of response to colchicine orally in some nonresponders could result from inadequate absorption or altered disposition of colchicine.