Patients with fibromyalgia syndrome (FMS) report chronic pain related to abnormal sensitivity of muscles that is reflected by so-called tender points (TP). TP represent areas of abnormal mechanical pain thresholds that have only shown a minor correlation with clinical pain of FMS patients and seem to be better suited for predicting distress. Pain-related negative affect (PRNA), abnormal temporal summation of second pain (termed wind-up or WU), and abnormal WU decay are frequently present in FMS patients. WU and WU decay can provide measures of central sensitization, which may contribute to clinical FMS pain. We therefore investigated the role of WU, WU decay, TP count, and PRNA as predictors of clinical pain in FMS subjects.Fifty-five FMS subjects rated their clinical pain at entry into the study using a visual analogue scale (VAS). After a TP evaluation, all subjects received two trials of thermal WU and WU decay testing. Hierarchical regression analysis demonstrated that the combination of PRNA ratings, TP count, and WU decay ratings predicted 49.7% of the variance of clinical pain in FMS. This model demonstrates independent relationships of biological and psychological factors to clinical pain and underscores the important role of abnormal peripheral and central pain mechanisms for FMS. Therefore, the combination of PRNA, TP count, and WU decay may provide an excellent measure for future clinical studies of FMS patients.