Background: Although many drugs are excreted by eccrine sweat glands, data in literature are insufficient when it comes to histopathological, histochemical and immunohistochemical aspects of involvement of the eccrine sweat gland apparatus in adverse cutaneous drug reactions (ACDRs). Objective: To describe histopathological changes in the eccrine sweat gland apparatus in different types of ACDRs in both lesional and non-lesional skin, to evaluate their secretory function histochemically using PAS/PAS diastase and to study immunohistochemically the expression pattern of CD8, Immunoglobulin M (IgM) and Carcinoembryonic Antigen (CEA) in this group. The study aims to find associations between the different histopathological, histochemical and immunohistochemical patterns and the different causative drugs and drug reactions. Methods: Forty patients with ACDRs were recruited. Patients were subjected to detailed clinical evaluation. Biopsies were taken and histopathological examination of routinely stained H&E sections was carried out for establishing a diagnosis and for detailed assessment of changes in the eccrine apparatus. Sections were also stained with PAS/PAS diastase and with monoclonal anti CD8, anti IgM and anti CEA antibodies. Results: Sweat gland changes in lesional skin were encountered in 97.5% of ACDRs cases, with secretory coils being the most frequently affected segment (89.5%), followed by distal ducts (87.5%), proximal ducts (60%) then acrosyringium (54.2%). Non-lesional skin was significantly less involved than lesional skin (P< 0.0001). The clinicopathological category of ACDR had no significant influence on the histopathological involvement of various segments of the sweat apparatus. Etiopathogenetic division of cases revealed that secretory coils were more significantly involved in the cell mediated than the immunoglobulin mediated group (P=0.048). Distal duct changes were more significantly encountered with the multiple medications group (P=0.008). Secretory function showed no significant difference when lesional and non-lesional skin was compared. IgM and CD8 showed higher expression in lesional versus non-lesional biopsies, with no significant difference between cell mediated and immunoglobulin mediated groups. No significant difference existed as regards CEA expression between lesional and non-lesional skin. Conclusion: The sweat apparatus is almost always implicated in ACDRs regardless of the entity. It is clearly shown that lesional skin is significantly involved than apparently normal skin. Based on the present findings it appears that the changes in the segments of the sweat apparatus in ACDRs are resultant of various products of the pathological process rather than a drug induced primary event.