Results of studies conducted to characterise local, systemic, reproductive, and mutagenic effects indicate that the new macrolide antimicrobial clarithromycin is well tolerated within reasonable multiples of the intended clinical dose. No adverse effects of clarithyromycin on male or female fertility, perinatal, or postnatal reproduction were indicated by data from rabbits, mice, rats and macaques. No evidence of mutagenic potential was revealed from various in vitro and in vivo study methodologies. Evidence of low potential for ototoxicity, oculotoxicity, hepatotoxicity and nephrotoxicity was provided in studies involving rats, dogs and primates. In agreement with studies with other macrolides, venous irritation potential for the intravenous lactobionate salt formulation was substantial in rabbit studies. In addition, the safety profile of this agent has been evaluated on the basis of adverse reactions and abnormal laboratory values seen in phase I, II and III international clinical trials conducted in adults. The most frequently reported adverse reactions occurring in 3768 patients receiving clarithromycin in phase II and III trials were nausea (3.8%), diarrhoea (3.0%), abdominal pain (1.9%) and headache (1.7%). Adverse reactions were not serious and were usually rapidly reversible. The incidence of adverse reactions did not vary with gender, race or age. Adverse reaction rates were comparable to or less than those of comparator beta-lactams and macrolides. Overall, clarithromycin appears to be a safe and well-tolerated macrolide antimicrobial agent.