The aim of this study was to investigate associations between thymic pathology and HLA in myasthenia gravis. HLA typing was performed in 95 of 125 Caucasian patients who underwent transsternal thymectomy for myasthenia gravis between 1976 and 1995. Multiple comparison procedures applied within each HLA locus demonstrated significant correlations between the ancestral suprahaplotype A1 B8 DRB1*0301 DRB3*0101 DQA1*0501 and thymic hyperplasia and between HLA-A24 and thymoma. A weaker association was found between A3 and thymic atrophy and thymolipoma. On logistic discriminant analysis, HLA-B8 (P = 0.001) and HLA-A3 (P = 0.028) were identified as the only significant classifiers to jointly provide a good discriminator between the thymic pathologies. When the suitability of HLA for detection of thymoma was examined in a second logistic regression analysis, both HLA-A24 (OR 9.7; 95% CI [1.6, 73.7]) and HLA-B8 (OR 0.1; 95% CI [0.0, 0.5]) were significant predictive factors. The above correlations between thymic pathology and HLA-A3, HLA-A24, and HLA-B8 (but not MHC class II alleles) suggest an involvement of MHC class I restricted T cells in myasthenic autoimmunity that may partially be reflected by thymic pathology.