Rectal administration of several different preparations of diazepam to a group of adult volunteer patients with epilepsy produced variable rates of absorption. Peak serum concentrations following 10 mg, 20 mg, and 30 mg of diazepam solution were achieved between 13-60 min, 10-120 min and 30-90 min, respectively. An experimental diazepam solid solution suppository had significantly better absorption characteristics compared with the commercially available Valium suppository. Diazepam solution 20 mg was administered rectally in 10 adult epileptic patients with frequent spontaneous interictal spikes in their EEG. A highly significant reduction in spike frequency was seen compared with placebo. The effect was most marked 10-20 min after administration of diazepam, when the mean spike count fell to 39 .+-. 35 SD percent of the control value (P < 0.01), and this corresponded with a mean serum diazepam level of 210 .+-. 125 ng/ml.