Seventeen of 30 patients with chronic vaginal candidiasis (CVC) of at least 5 years duration had varying degrees of menstrual problems and defective T lymphocyte function; 8 developed amenorrhea. In a group of 40 CVC patients, titers of autoantibodies to ovary, thymocytes, a T-cell line (CCRF-CEM), and a B-cell line (RN114) were significantly higher than those in 45 normal females (69 ± 3 vs. 5 ± 2, 70 ± 27 vs. 4 ± 2, 17 ± 6 vs. 4 ± 2, and 73 ± 24 vs. 8 ± 5, respectively, mean ± S.E.). Antibody titers to sperm, T-cell line HSB-2, and B-cell lines RAJI and BALL-1 were within the normal range. Significant correlations were found between anti- Candida, anti-ovarian, and anti-thymocyte antibody titers. Similar results were found for 6 patients with chronic mucocutaneous candidiasis (CMCC) and in serial samples obtained over a one-year period from a representative patient with both CVC and CMCC. The anti-T-lymphocyte antibodies in these patients were directed primarily against non-suppressor (predominantly helper) T cells. Absorption of the sera with either Candida cells, ovarian follicle cells, or thymocytes reduced all three antibody titers; absorption with sperm or B-cell lines did not alter the titers. These results suggest the presence of one or more cross-reactive antigens on ovarian follicle, T lymphocytes (especially the helper cell subpopulation), and Candida.