The apicomplexan parasite Plasmodium gallinaceum has not been much studied from the veterinary standpoint. Although it causes malaria in domesticated chickens, no effective drugs appear to be commercially available. A mixture of trimethoprim and sulphaquinoxaline (TMP/SQX, ratio 1:3), with a wide spectrum of activity against bacteria and coccidia, is here shown to be also efficacious against blood-induced P. gallinaceum malaria when administered therapeutically in the feed of chickens for 5-day periods, beginning on the day before infection, or on the day of infection, or up to four days after infection. Chickens were protected against mortality and reduction of weight gain. Three other criteria of efficacy, which showed good correlation with each other and also with the two commercial performance criteria, were the production of green diarrhoea (due to biliverdin), parasitaemia and reduced haematocrit values. When TMP/SQX treatments were initiated sooner than five days after infection, parasites were almost entirely eliminated from the blood, whereas treatments initiated later than four days after infection failed to protect birds against clinical disease. Birds protected by TMP/SQX against primary infection with P. gallinaceum were immune to clinical malaria when exposed to a severe blood-induced challenge of P. gallinaceum 28 days later.