Objectives. To investigate microvascular function using laser Doppler imaging (LDI) following response to hyperaemia, neurovascular reflex and iontophoresis in systemic sclerosis (SSc) in comparison with primary Raynaud's phenomenon (PRP) and age-matched controls. A secondary aim was to evaluate if SSc patients with a higher Medsger vascular score have lower endothelial responses. Methods. Twenty patients with SSc, 10 PRP and 17 controls were studied. Patients with SSc were scored using the vascular component of the Medsger severity scale. A baseline LDI scan was performed on the dorsal aspect of both hands. Digital responses were quantified following maximum hyperaemic response (MHR), contralateral vasoconstrictor response (CLVc) and iontophoresis with acetylcholine (Ach)-endothelial dependent and sodium nitroprusside (SNP)-endothelial independent. Mean blood flow was quantified over a standard region of interest. Results. MHR was lower in SSc patients compared with controls (P < 0.001). A similar trend was seen when comparing SSc with PRP although this did not reach significance (P = 0.07). CLVc and Ach/MHR were lower in SSc vs PRP (P < 0.05) and controls (P < 0.001). No difference was observed in MHR, CLVc and Ach/MHR between PRP and controls. Overall, SNP/MHR was similar in all the three groups. SSc patients with a higher Medsger vascular score had lower endothelial-dependent (P < 0.01) and independent (P < 0.05) responses. Conclusion. SSc patients have abnormal microvascular regulatory responses compared with PRP and controls. This study also suggests that the degree of endothelial dysfunction may be related to the degree of peripheral vascular involvement.