The aim of the present study was to investigate the efficacy and clinical tolerability of the specific leukotriene B₄ receptor antagonist VML295 in the treatment of stable plaque psoriasis. Immunohistochemical and flow cytometrical methods were used to assess the effects on inflammation and epidermal proliferation. VML295 in the treatment of chronic plaque psoriasis was shown to be safe and well tolerated. After treatment, there was a statistically significant difference between patients treated with VML295 and patients treated with placebo with respect to the leukotriene B₄‐induced CD11b up‐regulation on the cell surface of polymorphonuclear leukocytes derived from peripheral blood. Ex vivo CD11b up‐regulation in the VML295‐treated group was completely inhibited after 7 days of treatment (P= 0.001). This effect persisted until the end of the treatment period (P= 0.004 on day 15 and P< 0.0001 after 4 weeks), whereas CD11b up‐regulation in the placebo group remained unaffected. There was no statistically significant difference in the median psoriasis area and severity index between the treatment groups at the end of the treatment period. During treatment, no significant histological changes were observed in the markers for cutaneous inflammation and epidermal proliferation. Although not statistically significant, a tendency for the increased expression of some markers of cutaneous inflammation and epidermal proliferation was observed after 1 week of treatment with VML295, and a decreased expression of these markers was seen after 4 weeks of treatment with VML295. This observation could indicate anti‐inflammatory effects of VML295 appearing between 2 and 4 weeks after the start of treatment.