Palmoplantar psoriasis (PPP) is a chronic, disfiguring condition, and its management is difficult. The systemic side effects of methotrexate can be avoided if it is effective topically. We studied the efficacy and safety of a recently marketed topical methotrexate (0.25%) preparation in a hydrogel base in patients with palmoplantar lesions. A total of 14 adult patients diagnosed clinically as plaque type of palmoplantar psoriasis (>30% of the palm and/or sole areas involved) were included in the study. Topical methotrexate 0.25% in a hydroxygel base was applied twice daily to the lesions for twelve weeks. The lesions were assessed for degree of erythema, scaling, induration and fissuring (ESIF) and were scored on a severity score of 0-3 (0--clear, 1--mild, 2--moderate, 3--severe) every two weeks. The most severe condition was given 12 points; 0 denoted no disease. The response at the end of the study was graded as minimal if there was up to 25% reduction in the EISF score, mild as 26-50% reduction, moderate improvement as 51-75% reduction in score, and marked improvement as >75% reduction in score. The average age of the 11 male and female patients was 41.5 years (18-57 years) with the duration of the disease varying from 2 months to 15 years. Ten patients had both palmar and plantar lesions; two each had only palmar lesions or plantar lesions. The ESI score at baseline was 5.8 +/- 0.9 for the palms and 6.8 +/- 0.5 for the soles. The scores at the end of the study were 3.5 +/- 0.7 for palms and 4.8 +/- 0.2 for the soles. The average time taken for improvement was at least six weeks. None of the patients had complete clearance of lesions. The drug was well tolerated by all patients. Methotrexate 0.25% in a hydrophilic gel is well tolerated but is not very effective in controlling the lesions of psoriasis on the palms and soles. A higher concentration in a different base with better penetration could possibly provide better results.