A multi-criterion algorithm for automatic delineation of small pulmonary nodules on helical CT images has been developed. In a slice-by-slice manner, the algorithm uses density, gradient strength, and a shape constraint of the nodule to automatically control segmentation process. The multiple criteria applied to separation of the nodule from its surrounding structures in lung are based on the fact that typical small pulmonary nodules on CT images have high densities, show a distinct difference in density at the boundary, and tend to be compact in shape. Prior to the segmentation, a region-of-interest containing the nodule is manually selected on the CT images. Then the segmentation process begins with a high density threshold that is decreased stepwise, resulting in expansion of the area of nodule candidates. This progressive region growing approach is terminated when subsequent thresholds provide either a diminished gradient strength of the nodule contour or significant changes of nodule shape from the compact form. The shape criterion added to the algorithm can effectively prevent the high density surrounding structures (e.g., blood vessels) from being falsely segmented as nodule, which occurs frequently when only the gradient strength criterion is applied. This has been demonstrated by examples given in the Results section. The algorithm's accuracy has been compared with that of radiologist's manual segmentation, and no statistically significant difference has been found between the nodule areas delineated by radiologist and those obtained by the multi-criterion algorithm. The improved nodule boundary allows for more accurate assessment of nodule size and hence nodule growth over a short time period, and for better characterization of nodule edges. This information is useful in determining malignancy status of a nodule at an early stage and thus provides significant guidance for further clinical management.