A group of p-substituted anilines were tested on their activities to form cytochrome P450 metabolic intermediate complexes with untreated or phenobarbital-induced rat hepatic microsomes. The Fisher's linear discriminant analysis method was used to study their structure-activity relationship. Results showed that the p-substituted anilines were correctly categorized except for 4,4'-diamino-diphenyl ether which interacted with phenobarbital-induced rat hepatic microsomes. The p-substituted anilines with greater lipophilicity and stronger electron drawing facilitated the formation of cytochrome P450 metabolic intermediate complex. The rat hepatic microsome induced by phenobarbital had greater activity in forming cytochrome P450 metabolic intermediate complex with p-substituted aniline than untreated rat hepatic microsome.