The effects of promethazine hydrochloride have been investigated in a rabbit kidney allograft model. The drug was ineffective on its own, but if added to a protocol that induced partial suppression of rejection in 50% of recipients, its effect was dramatic. Allograft survival was prolonged from a control mean of 10.3 days to a mean of 26.3 days. One animal survived 2 1/2 months, and no other drug than promethazine was given after day 6. Promethazine and 6-methylprednisolone alone also prolonged allograft survival, but the results were significantly better if the recipient had been exposed to donor blood before grafting. The results suggest that promethazine is a useful adjuvant immunosuppressive drug. It could be beneficial in man.