Midazolam is a water-soluble benzodiazepine proven to be efficacious in sedation, hypnosis, and induction and maintenance of anesthesia. Because of its water solubility, it is a desirable drug for the control of status epilepticus when intravenous (IV) access is not obtainable. This study compares intramuscular (IM) versus IV routes of administration of midazolam in the control of tonic-clonic activity produced by chemically induced generalized seizures in a swine model. When midazolam was administered by IV route, tonic-clonic activity lasted a mean of 34 +/- 5.4 seconds, and when administered by IM route, the tonic-clonic activity lasted a mean of 116 +/- 41 seconds. Both were considerably abbreviated when compared with the expected duration of pentylenetetrazol-induced seizures in the swine model. Serum levels of midazolam achieved by the IV route were considerably higher than those achieved by the IM route. It is concluded that midazolam is effective in the control of tonic-clonic manifestations of generalized seizures when administered by the IV or the IM route and that no correlation exists between serum levels achieved and the time to control the seizure.