The ability of interleukin 4 (IL4), administered subcutaneously around the cutaneous lesion in the form of hydrophilic gels, to affect the development of established Leishmania major infections in the BALB/c mouse was studied. IL4 had a therapeutic effect on L. major lesion growth compared with control mice, causing not only resolution of the parasite lesions over a period of 10 weeks but also rendering animals resistant to reinfection. Adoptive transfer of splenic T cells, obtained from IL4-treated animals, conferred significant resistance to L. major infection in naive BALB/c mice compared with controls. These results demonstrate that IL4 is capable of not only reversing the usual (i.e. non-curing) course of L. major infection in the BALB/c mouse, but also of promoting the generation of protective immunity. The nature of the gel used to deliver the cytokine was found to be important since the therapeutic activity of IL4 in poloxamer gel was not observed when a hydroxypropylmethyl cellulose (hypromellose) gel was used as the IL4 vehicle.