A 52-week toxicity study by oral administration (capsule) was performed in beagle dogs with nefiracetam (N-(2,6-dimethylphenyl)-2-(2- oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7), a new cognition-enhancing agent, as a part of a safety evaluation program. Dosages of 0 (control), 10, 30 and 90 mg/kg/d were selected for this study. Treatment-related findings were confined to the 90 mg/kg/d level and indicated the kidney and the testis as the main target organs for toxicity. Signs of systemic toxicity, as indicated by the laboratory investigations, were not apparent until the second half of the study and included the principal findings of higher urea nitrogen, and creatinine, with higher urinary volumes and corresponding lower specific gravity, osmolarity and protein values. The microscopic pathology examination showed various changes at the renal papilla, collecting ducts, and medullary and cortical scarring. This examination also revealed decreased spermatogenesis in the testes, with associated decreased numbers/absence of spermatozoa in the epididymides. At the 30 mg/kg/d level, the minor microscopic pathology changes seen in the kidneys of one male animal were considered to be of equivocal toxicological importance. There were no treatment-related findings at the low dosage level (10 mg/kg/d) and, therefore, this level was considered as the non-toxic effect level of nefiracetam.