The aims of the study were to describe and compare the frequency and nature of histologically detectable microvascular lesions in patients with various connective tissue diseases (CTD). An electron microscopic examination of specimens obtained by the technique of capillaroscopically guided nailfold biopsy was performed in 52 patients with CTD [nine systemic lupus erythematosus (SLE), eight mixed CTD, 18 scleroderma, 17 undifferentiated CTD] and 27 controls. The microvascular changes most frequently observed by electron microscopy were multilayering of the basal lamina (approximately 70% of the CTD patients), an increased amount of perivascular connective tissue, perivascular oedema formation, and an increased number of perivascular fibroblasts and mast cells (each in 30-37% of the CTD patients). In contrast, no particular histopathological feature was found in > 25% of the controls, multilayering (22.6%) being the most frequently observed. Comparing the different conditions studied, there were distinct differences in the frequency and nature of the histologically observed microvascular changes. In particular, SLE seems to be based on a separable type of vasculopathy consisting of significantly less frequent microvascular abnormalities. In conclusion, ultrastructural abnormalities of the microvascular system are a frequent finding in CTD. Electron microscopic examination of specimens obtained by capillaroscopically guided nailfold biopsy is able to disclose histopathological differences between defined entities. Therefore, this approach may be a useful tool to gain further insights into potentially separable aetiopathological mechanisms of the various types of CTD.