Alpha-iso-methylionone (AIM), a fragrance ingredient, was evaluated for systemic toxicity in rats. Male and female Sprague Dawley rats were administered 0, 5, 30, or 500 mg/kg/d AIM via gavage for 90 days. Statistically significant changes in blood chemistry parameters (reduced aspartate aminotransferase [AST], and increased cholesterol, creatinine, and total protein) were observed in both sexes at 500 mg/kg/d. There were statistically significant increases in liver and kidney weights in both sexes and in spleen weights in males at 500 mg/kg/d. Adaptive hepatocyte enlargement was observed in both sexes at 500 mg/kg/d. Globular accumulations of eosinophilic material were observed in the renal tubular epithelium in males at ≥30 mg/kg/d. Thyroid and bone marrow histopathological changes were observed in males at 500 mg/kg/d. The no-observed-effect level was 5 mg/kg/d for males and 30 mg/kg/d for females. Based on histopathological changes in the kidney in males, the no-observed-adverse-effect level was 30 mg/kg/d.