Calmodulin is a calcium-binding receptor protein that regulates the contractile protein systems of skeletal muscle and platelets. The levels of platelet calmodulin were measured in twenty-seven adolescents to determine whether there was a relationship between these levels and the progression or the severity of idiopathic scoliosis. The study included seventeen patients who had idiopathic scoliosis of varying severity and patterns and a control group consisting of ten age and sex-matched subjects: eight patients who were being managed for non-scoliosis-related problems and two normal volunteers. Platelets were isolated from the venous blood of all adolescents. The platelets were homogenized and centrifuged, and the calmodulin-containing supernatant was isolated. The level of calmodulin was then measured with use of a radioimmunoassay that employs competitive binding between native, unlabeled calmodulin and I-125-labeled calmodulin. The results showed that the level of platelet calmodulin in the patients who had a progressive curve (more than 10 degrees of progression in the previous twelve months) (3.83 nanograms per microgram of protein) was significantly higher than the level in the patients who had a stable curve (less than 5 degrees of progression in the previous twelve months) (0.60 nanogram per microgram of protein) (p < 0.01); the levels in the stable group and the control group (0.69 nanogram per microgram of protein) were similar. The level of platelet calmodulin appeared to be an independent and possibly more acute predictor of progression of the curve than the Risser sign alone. In the patients who had a Risser sign of 0 or 1 and a progressive curve, the average level of platelet calmodulin was 4.42 nanograms per microgram of protein, compared with 0.69 nanogram per microgram of protein in the patients who had a Risser sign of 0 or 1 and a stable curve and 0.65 nanogram per microgram of protein in those who had a Risser sign of between 2 and 5. A single determination of the level of platelet calmodulin did not predict the degree of curvature of the spine (Pearson correlation coefficient, r = 0.30). CLINICAL RELEVANCE: The level of platelet calmodulin appears to be a useful predictor of progression of the curve in patients who have adolescent idiopathic scoliosis. If future longitudinal studies corroborate our results, these levels could be used clinically to avoid unnecessary irradiation in patients who have a low risk of progression of the curve and to predict more accurately the need for management with a brace or operative intervention, or both, in patients who have a high risk of progression.