In this study the leukocyte alkaline phosphatase (LAP) score in 106 patients with multiple myeloma (MM) in various phases of the disease (66 at diagnosis, 18 in plateau phase, 22 in relapse) was examined and compared with the score of 68 patients with monoclonal gammopathy of undetermined significance (MGUS) and 53 normal volunteers. In addition, the circulating levels of granulocyte-colony stimulating factor (G-CSF) were measured to explore the possible involvement of this cytokine in the pathogenetic mechanisms that lead to increased LAP activity. The results showed that the mean LAP score in patients with MGUS was comparable to normals and significantly lower than in MM (p < 0.001). Also, it increased with increasing tumor mass, and was lower in myelomas with stable disease than in those with active disease. G-CSF concentrations closely mirrored the behaviour of LAP score (r = 0.850, p < 0.001), significantly differing between each group of individuals. Its mean levels in MGUS were comparable to those of controls, whereas they were significantly increased in MM (p < 0.001), again with escalating values from cases with low tumor mass to advanced stages, and with lower concentrations in patients in plateau phase than in those in relapse. A significant correlation was found between G-CSF and neopterin levels (r = 0.578, p < 0.001), thus indicating an origin of the cytokine from monocytes and macrophages. These findings suggest that LAP scoring may assist in distinguishing benign from malignant paraproteinemias and may be used to follow the progression of plasma cell neoplasias.(ABSTRACT TRUNCATED AT 250 WORDS)