A histochemical and biochemical study of the reactions of Wistar rats and New Zealand rabbits to Streptococcus pyogenes, type 12, strain H-8, and the nephrotoxin (NT) elaborated by these organisms is presented. A significant lactic dehydrogenase (LDH) increase was found in the sera of all test rats 27 days following treatment with streptococcal NT. However, before this increased activity was detected, a marked decrease in LDH activity was obtained as early as 1 day after the last NT injection. This decrease was modest in rats treated with 1.0 mg NT, but it was great when the dosage of NT was increased to 5.0 mg. Serum LDH values also decreased progressively, up to about 2 weeks, in rabbits infected with nephritogenic streptococci or treated with streptococcal nephrotoxin. Such serum LDH fluctuations did not occur in animals treated with saline or Todd–Hewitt broth. Histochemical studies also suggested an initial inhibition by NT of LDH activity in renal tissue.