Objective To examine digital microvascular responses in patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and compare these to the responses in healthy control subjects. Methods Digital microvascular responses to repeated episodes of iontophoresis of acetylcholine chloride (endothelial-dependent), sodium nitroprusside (endothelial-independant) and adrenaline were measured using dual-channel laser Doppler in 8 healthy control subjects, 8 patients with PRP and 8 patients with SSc. Results There were no significant differences in responses between groups. For each chemical the greatest response was generally seen in period 7 of the protocol (after the third episode of iontophoresis). For acetylcholine chloride in period 7, the age and baseline adjusted ratio of the maximum response of PRP to control was 0.93, 95% CI (0.26, 3.38) and for SSc to control it was 0.60, 95% CI (0.13, 2.81). For sodium nitroprusside in period 7, this age and baseline adjusted ratio of the maximum response of PRP to control was 1.31, 95% CI (0.74, 2.32) and for SSc to control it was 1.35, 95% CI (0.68, 2.67). For adrenaline in period 7, the age and baseline adjusted ratio of PRP to control was 1.51, 95% CI (0.79, 2.89) and for SSc to control it was 2.18, 95% CI (1.01, 4.69). Conclusion This study demonstrates the usefulness of iontophoresis of vasoactive chemicals, combined with laser Doppler blood flowmetry, in the non-invasive assessment of dermal microvascular responses. One possible explanation for the lack of difference in responses between groups is that vasoactive chemicals other than those discussed are important in the pathophysiology of primary and secondary Raynaud's phenomenon.