A consecutive series of 99 untreated patients undergoing radical surgical resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our purpose was to analyze the predictive relevance of proliferative variables studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected mitotic (M/V) index, and S-phase fraction (SPF)] on clinical outcome in relation to DNA ploidy and clinicopathological features. All of the patients were followed up for a median of 32 months (range, 5-58 months). A weak, but significant, positive correlation was found between M/V and PCNA indices (except the PCNA weighted mean index:labeling index ratio) or these indices and SPF. At univariate analysis, node positivity (P < 0.05), poor histological grade (P < 0.01), DNA aneuploidy (P < 0.01), a high SPF (P < 0.01), and a high M/V index (P < 0.05) proved to be related significantly to quicker relapse, whereas T4 (P < 0.05), subglottic site (P < 0.05), DNA aneuploidy (P < 0.01) and a high SPF (P < 0.01) were related significantly to shorter overall survival. With multivariate analysis, a high SPF (> 12.1%) and histological grade (G3) were related to the risk of relapse (relative risk, 8.65 and 5.45, respectively), whereas only a high SPF was related independently to the risk of death (relative risk, 7.30). Our study has identified SPF, in addition to histological grade, as an important biological indicator in laryngeal carcinomas.