Abdominal pain and diarrhea are frequent side effects of chronic colchicine therapy. Drug-induced lactose deficiency has been demonstrated in the experimental animal. Lactose malabsorption was assessed by the lactose breath test in 23 patients with familial Mediterranean fever (FMF) receiving colchicine for 0.25-15 years (mean 3.16). Twenty FMF patients not receiving colchicine and 38 non-FMF lactose malabsorbers served as controls. Patients receiving colchicine had a significantly higher percentage of lactose malabsorption (20/23, 87%) versus nontreated FMF patients (13/20, 65%; P < 0.05). Lactose intolerance was also more prevalent in colchicine-treated patients (17/23, 74%) versus nontreated FMF (5/20, 25%; P < 0.0005) and control lactose malabsorbers (16/38, 42%; P < 0.01). Of the 12 patients investigated before and 3 months after colchicine administration, 7 showed induction or aggravation of lactose malabsorption. The lactose-free diet resulted in partial improvement of symptoms. Colchicine induces significant lactose malabsorption in FMF patients and this is partially responsible for the gastrointestinal side effects of the drug.