This case-control study evaluated the relation between potential exposure to chemical and physical agents and the occurrence of intracranial tumors among employees at a petrochemical research facility. Cases were employees with glioma (n = 6) or benign intracranial tumors (n = 6). Controls (n = 119) were individually matched to cases on gender and birth year, and they were alive and did not have an intracranial tumor at the case's diagnosis date. Exposure information came from interviews with subjects or surrogates and from corporate records on agents used in research projects. Analyses computed matched odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for self-reported exposure to 15 agents and project-based estimates of exposure to 29 agents. For gliomas, the OR was elevated for self-reported exposure to ionizing radiation (OR, 15.7; CI, 1.4 to 179.4), n-hexane (OR, ∞ CI, 1.4 to ∞), organometallics (OR, 9.4; CI, 1.5 to 59.7), and amines other than nitrosamines (OR, 6.0; CI, 1.0 to 35.7). The OR also was elevated for project-based potential use of ionizing radiation (OR, 9.6; CI, 1.7 to 55.2) and for potential use of n-hexane lasting at least 4 years (OR, 16.2; CI, 1.1 to 227.6). For benign intracranial tumors, the OR was elevated only for self-reported exposure to ionizing radiation (OR, 5.4; CI, 1.7 to 43.1) and other amines (OR, 5.2; CI, 0.9 to 29.5). Occupational exposure may have contributed to the glioma excess, but the specific causal agents remain unknown. The study indicated that benign intracranial tumors were unlikely to be work-related.