IGF-I receptor (IGFR) content and its prognostic significance were evaluated in human breast cancer specimens using a sensitive and specific radioimmunoassay (V. Pezzino et al., Metabolism, 40: 861, 1991). The prognostic significance of IGFR expression was investigated by two different approaches: (a) detectable IGFR content was measured in 82% of specimens in a consecutive series of 184 human breast cancers and in 32% of 19 normal breast tissues. The average IGFR content in breast cancer was nearly 10-fold higher than the value observed in normal breast tissue (7.6 +/- 0.8 versus 0.8 +/- 0.1 ng/0.1 mg protein, mean +/- SEM; P < 0.001). IGFR content was positively correlated with estrogen (ER) and insulin receptor content (r = 0.269 and 0.515, respectively, Pearson correlation) but not with progesterone receptors (PR). No significant correlation was observed between IGFR content and a variety of tumor parameters (tumor size, lymph node involvement, grade) and host characteristics (age, body mass index, menopausal status); (b) IGFR content was measured in a noncontinuous series of 265 primary breast cancer specimens subdivided into 136 high-risk and 129 low-risk specimens on the basis of being either negative (ER-/PR-/aneuploid/high S-phase) or positive (ER+/PR+/diploid/low S-phase) for four well-established prognostic factors. IGFR levels were significantly higher in the low-risk group (6.4 +/- 0.4 ng/0.1 mg protein, mean +/- SEM) than in the high-risk group (3.6 +/- 0.5; P < 0.0001, Wilcoxon sum rank test). In summary, our data indicate that there is an elevated IGFR content in most human breast cancers compared with normal breast tissue and that an elevated IGFR content is a favorable prognostic indicator.