The fundamental frequency (F0) characteristics of 19 male patients with advanced laryngeal cancer, treated with cisplatin-based chemotherapy as part of a Larynx Preservation Protocol (LPP), were measured before each of three cycles of chemotherapy received before definitive radiotherapy (RT). In these select patients, for whom chemotherapy resulted in > or = 50% decrease in the tumor bulk, it was found that mean F0 was essentially unaffected by the disease and did not change over the course of chemotherapy, although the cycle of their treatment could be differentiated by both speaking F0 variability (pitch sigma) and F0 perturbation (jitter). Although these measures failed to distinguish between those patients showing a complete response (CR) (no measurable disease) versus a partial (PR) (residual) tumor response at the primary disease site, the significant changes observed in both groups indicate that frequency variation measures could prove valuable in the documentation of tumor response to nonsurgical therapeutic intervention if the voice is directly affected. Additional assessment of 15 age- and disease-matched patients who showed minimal or no primary response to the chemotherapy showed no significant change in any of the frequency measures after one chemotherapy cycle, suggesting that vocal improvement seen in the successful chemotherapy patients was not due to postbiopsy healing or other systemic influence unassociated with tumor reduction.