The epileptogenic properties of 10 cephalosporins and penicillin G were compared by intraventricular application to rats. At doses greater than 32 micrograms per head, cefazolin provoked tremendous seizure signs, a spike-and-wave complex appeared in close succession for more than 30 min, and severe convulsions were observed repeatedly. Reactions to cefotiam, ceftezole, and cephaloridine were almost equal to reactions to penicillin. No epileptogenic signs were observed on EEGs, and no behavioral symptoms were observed after administration of 1,000 micrograms of cephalexin and cephradine per head. Reactions to cephapirin, cefmetazole, cephalothin, and ceftizoxime exhibited less marked epileptogenic features; activity was diminished in that order on EEGs and in behavioral signs. Compounds substituted with two different heterocyclic rings at position 7 (R1) and position 3 (R2) of 7-aminocephalosporanic acid were potent in producing epileptogenic signs both on EEGs and in behaviors. Compounds substituted with a heterocyclic ring at either position of 7-aminocephalosporanic acid were less potent. Compounds such as ceftizoxime, cephalexin, and cephradine, substituted at R2 with small groups, were almost incapable of producing epileptogenic activity. This may indicate that the substitution of a heterocyclic ring at position 3 will provoke the convulsive actions.