The prognostic significance of argyrophilic nucleolar organizer regions (AgNORs) has been evaluated in bone marrow trephine biopsies from 64 patients with multiple myeloma (MM) prior to therapy. The univariate Kaplan-Meyer survival analysis showed a significant correlation between survivals and AgNOR counts (median of survival 51.3 months for cases with < or = 4.62 AgNORs per plasma cell (PC) versus 16 months for cases with > 4.62 AgNORs per PC; P = 0.0000) or AgNOR distribution in PC nucleus (AgNOR configuration) (median of survival 71.67 months for cases with tightly grouped AgNORs, 16.26 for partially grouped and 11.74 for dispersed AgNORs; P = 0.001). Significant prognostic correlations were also found for monoclonal immunoglobulin type (P = 0.008), platelet counts (P = 0.0078), serum creatinine level (P = 0.0001), Durie's clinical stage (P = 0.02), percentage of plasma cells in bone marrow biopsies (BMPC%) (P = 0.005), pattern of medullary involvement (P = 0.003) and PC atypia (P = 0.009). Borderline result was detected for the percentage of PCs in aspirates (P = 0.06). No significant correlation was found between prognosis and patients age, sex, haemoglobin level, serum albumin or calcium level, marrow cellularity and excess of haemosiderin. Multivariate survival analysis showed that only two variables were significantly correlated with prognosis: AgNOR counts (P = 0.003) and AgNOR configuration (P < 0.001). In addition, the analysis of variance showed significant association between AgNOR number and platelet counts, haemoglobin level, calcaemia, creatininaemia, clinical stage, percentage of PCs in aspirates, BMPC%, pattern of medullary involvement, PC atypia, marrow cellularity and configuration of AgNORs. Our results indicate that AgNOR counts and configuration have prognostic and diagnostic value and therefore they are useful independent parameters to assess the pretherapeutic aggressiveness of multiple myeloma.