Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a potential tracer in patients with multiple myeloma (MM). The aims of this study were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake in patients with MM, to assess their relationship with clinical status and stage of disease, and to try to clarify the meaning of the diffuse bone marrow uptake of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine of these patients had active disease (13 in stage I, ten in stage II, and six in stage III) and ten were in remission after chemotherapy. Anterior and posterior whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc-MIBI. The scans were classified as showing: pattern N, when only physiological uptake was present; pattern D, when diffuse bone marrow uptake was observed; pattern F, when areas of focal uptake of the radiotracer were evident; or pattern D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was scored according to extension and intensity. Seven of the 39 patients (18%) showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F. Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or D+F), 29 (91%) had active disease. Only three patients in remission showed pattern D, but with a very low bone marrow uptake score. Both extension and intensity of diffuse bone marrow uptake correlated with the amount of the monoclonal component and the percentage of bone marrow plasma cells. The distribution of the 99mTc-MIBI uptake patterns differed among patients in different stages of disease. Using as criteria for advanced stage the presence of either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%) diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. The presence of focal uptake or of intense diffuse bone marrow uptake suggests that the patient has active and advanced stage disease, while a negative scan in a patient with MM clearly indicates remission.