Blood lymphocyte responses to Candida protein antigen (CP, Candida mannan mitogen (CM) and Staphylococcus aureus protein A (SPA) were followed in 133 bone marrow transplant (BMT) recipients. Lymphocyte proliferative responses to CP and SPA normalized within 6-12 months. The response to CM was only decreased in non-colonized patients during the first 2 months post-BMT and had already returned to normal by 1 month in colonized patients. During the forthcoming years all three lymphocyte stimulatory tests responses reached donor levels. There was a tendency for low lymphocyte reactivity to CP, high reactivity to CM and equal reactivity for SPA among recipients of T cell-depleted marrows as compared to patients with conventional graft-versus-host disease (GVHD) prophylaxis. After BMT, patients who were colonized with Candida recovered and increased their lymphocyte response to CP and CM within 1-3 months, while non-colonized patients required more than 6 months to regain normal stimulatory capacity. Patients who developed grades II-IV acute GVHD had significantly higher pretransplant lymphocyte responses to both CP (p = 0.02) and CM (p = 0.02) than patients with grades 0-I acute GVHD. There was also a trend for patients who later had a confirmed invasive Candida infection to have high responses to CP before BMT (p = 0.07). After BMT, stimulation by CM, CP and SPA was not affected by acute or chronic GVHD or cytomegalovirus. In conclusion, proliferative capacity to Candida is restored early after BMT and superficial fungal colonization seem to be of importance for this maturation.