Thirty-two children affected by juvenile rheumatoid arthritis (JRA) were studied with serial measurements of bone mass for an average of 18 months, to evaluate the effects of long-term methotrexate (MTX) treatment on bone. Bone mineral density (BMD) was measured on lumbar spine and total body. During MTX therapy some increase in BMD was observed, though this was smaller than in a control group of healthy children. Axial (spine and trunk) and appendicular (upper and lower limbs) BMD showed similar increases. BMD, either as an absolute value or as a percent variation from baseline, did not correlate with either MTX dose or length of therapy. In children treated also with corticosteroids, these drugs negatively influenced bone mass increase. The main determinant of absolute spine BMD value appeared to be weight, while height and lean mass seemed to be the determinants of total body BMD. Pubertal stage and disease activity significantly influenced the yearly change in BMD. In conclusion, our data suggest that long-term, low-dose therapy with MTX does not induce osteopenia in children with JRA.