In 30 patients with multiple myeloma (MM) and mild to moderate anaemia (mean Hb 107 g/1, 95% confidence limit (CL) 102–113) but no evidence of renal failure (serum creatinine<110μmol/1), serum erythropoietin (EPO) showed significant inverse logarithmic correlation with the haemoglobin level (r=–0.57,p= 0.001). The observed/expected ratio of log-EPO in patients with MM (mean 0.96, CL 0.89–1.04) was similar to that of 119 subjects (mean 1.01, CL 0.96–1.05) with or without anaemia (mean Hb 116 g/L, CL 110–121) but without renal failure. The concentration of circulating erythroid progenitors (BFU-E) in 10 MM patients in plateau phase was significantly reduced (mean 0.70×105/l of Blood, CL 0.34–1.06) compared to that of 8 normal controls (mean 3.57, CL 1.60–5.55,p= 0.011)In vitrosensitivity of the BFU-E to EPO in the patients with MM was comparable to that of the normal controls. It appears that in MM there is an appropriate EPO response to anaemia but even in the plateau phase the number of circulating BFU-E is reduced, reflecting a degree of marrow failure. However, the progenitors are normally sensitive to EPO in such patients, and therapeutic doses of EPO may correct the anaemia by a pharmacological rather than a physiological effect.