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Three antigens of Candida albicans were comparatively evaluated to their ability to elicit delayed hypersensitivity (DH) responses in the mouse footpad test, using alloxan-diabetic and normal mice which were primed with heat-killed C. albicans in complete Freund adjuvant. These antigens were: (1) a preparation of sonically disrupted heat-killed cells; (2) a preparation of soluble cytoplasmic material remaining in the supernatant of a broken-cell suspension centrifuged at 100,000 g; (3) a preparation obtained by extraction of pulverized defatted cells with dilute phenol and sodium bicarbonate in water. After separation by polyacrylamide gel electrophoresis, the major components of soluble cytoplasmic material and dilute phenol extract were identified as a 43-kD protein, and glycoproteins of 21, 27 and 38 kD, respectively. Fifty-eight CD-1 outbred mice, which had received a single intravenous injection of alloxan followed by a 28-day rest period, were randomized with normal littermates to distinct experimental groups. Seven days after sensitization, mice were injected with one of the antigens in the right rear footpad and saline in the left rear footpad and the net specific increase in footpad thickness determined 24 and 48 h later. All three antigens elicited significant responses in sensitized normal mice. The responses of sensitized diabetic mice were clearly inferior to those of sensitized normal mice when heat-killed cells and soluble cytoplasmic material were used. Dilute phenol extract elicited equivalent responses at 24 and 48 h in both primed diabetic and normal mice.