The creatine kinase (CK) method, which is based on difference in CK activity at injection sites and in control tissue, was used for quantitation of local tissue damage after intramuscular injection of varying volumes and preparations in rabbits and pigs. Injections were given in the central part of the longissimus dorsi muscle. Three days after the injections the animals were killed and the arbitrary amounts of tissue without CK were calculated from the CK activity in muscle tissue at the injection sites and in control tissue. Determination of tissue damage by the CK method was in good agreement with macroscopic and microscopic changes, whether a well demarcated necrotic area or little or no necrosis was found at the injection site. Tissue damage was proportional to injection volumes between 0.25 and 1 ml in rabbits and 0.5 and 3 ml in pigs. In rabbits tissue damage per injected ml was found to be more than twice the damage seen in pigs. It is concluded that the CK method is a reliable method for quantitation of local tissue damage after intramuscular injections and that injection of even small volumes of 0.25-0.5 ml in the longissimus dorsi muscle of rabbits is a sensitive test of the local toxicity of drugs.