Benign and malignant brain tumors and normal cerebral cortex were assayed for calmodulin content by enzymatic and radioimmunoassay techniques. Normal cerebral cortex contained more (8.31 +/- 1.27 vs 3.30 +/- 0.42 micrograms/mg protein) calmodulin than the brain tumors. The contents of calmodulin in the malignant glioblastomas were significantly higher than the meningiomas (5.41 +/- 0.31 vs 2.97 +/- 0.16 micrograms/mg protein). These differences were independent of tumor location and persisted when calmodulin content was normalized for DNA rather than protein content. This data supports differences in the tissue calmodulin contents with normal cortex greater than primary malignant tumors greater than benign tumors greater than metastatic tumor tissue.