Renal failure (RF) occurring in the course of multiple myeloma is often judged irreversible and generally considered an ominous complication. The aim of the present study was to re-evaluate the outcome, triggering conditions and prognostic factors of severe RF in a series of 34 patients, 33 to 90 years old. RF was totally reversible in 7 patients and partially reversible in 9 although 6 of them had to be temporarily dialyzed. However, the improvement in renal function was often very slow as indicated by an average recovery time of 115 days. The high rate of RF reversibility was associated with markedly lengthened survival. Review of triggering events confirmed the leading role of dehydration and hypercalcemia, but further suggested that intake of nonsteroidal anti-inflammatory drugs and renal infection might play a part in the development of RF. Systematic statistical analysis of potential prognostic factors showed that the outcome was significantly more severe in females, but age, myeloma characteristics including tumor mass, calcemia, and triggering events had no predictive value. The most reliable prognostic indicators were provided by analysis of kidney biopsy performed in 30 patients. Complete recovery from RF was observed only in the absence of global tubular atrophy and interstitial damage. In contrast, cast-induced tubular obstruction detected by the presence of Tamm-Horsfall protein in urinary space of glomeruli did not seem to influence the outcome of RF. Finally, we analyzed the prognostic value of immunochemical properties of light chains (LC). Lambda LC were unexpectedly detected in 2 of 3 patients, as compared to a ratio of 1 to 3 in the population of normal and monoclonal Ig, but LC type did not correlate with the course of RF. Isoelectric points of LC measured in 32 patients were dispersed from 5.2 to 8.9 and bore only weak prognostic significance. These results underline the value of kidney biopsy and justify aggressive treatment including dialysis and chemotherapy.