Inasmuch as leukocytes were reported to be an active pharmacologic compartment, colchicine disposition was determined in plasma, granulocytes, and mononuclear cells in healthy volunteers after 1 mg oral single and multiple doses. After the single dose, maximal colchicine concentration was observed at 1 hour in plasma and 47 hours later in leukocytes. This delay was confirmed by the slow accumulation of colchicine by lymphocytes in culture. In the multiple-dose study, mean granulocyte colchicine concentration (20 to 53 ng/10(9) cells) were twofold higher than in mononuclear cells (9 to 24 ng/10(9) cells). Mean predicted colchicine multiple-dose granulocyte and mononuclear cell concentrations were 2.5-fold and ninefold higher, respectively, than those measured. After the last dose, colchicine decreased, with half-life values between 41 and 46 hours for leukocytes and 49 hours for plasma. This study validates leukocytes as a microcompartment whose kinetics correlates with colchicine biologic effects.