Image segmentation remains one of the major challenges in image analysis. In medical applications, skilled operators are usually employed to extract the desired regions that may be anatomically separate but statistically indistinguishable. Such manual processing is subject to operator errors and biases, is extremely time consuming, and has poor reproducibility. We propose a robust algorithm for the segmentation of three-dimensional (3-D) image data based on a novel combination of adaptive K-mean clustering and knowledge-based morphological operations. The proposed adaptive K-mean clustering algorithm is capable of segmenting the regions of smoothly varying intensity distributions. Spatial constraints are incorporated in the clustering algorithm through the modeling of the regions by Gibbs random fields. Knowledge-based morphological operations are then applied to the segmented regions to identify the desired regions according to the a priori anatomical knowledge of the region-of-interest. This proposed technique has been successfully applied to a sequence of cardiac CT volumetric images to generate the volumes of left ventricle chambers at 16 consecutive temporal frames. Our final segmentation results compare favorably with the results obtained using manual outlining. Extensions of this approach to other applications can be readily made when a priori knowledge of a given object is available.