The goal of this work is to investigate, for a large set of patients, the motion of the heart with respiration during free-breathing supine medical imaging. For this purpose we analyzed the motion of the heart in 32 non-contrast enhanced respiratory-gated 4D-CT datasets acquired during quiet unconstrained breathing. The respiratory-gated CT images covered the cardiac region and were acquired at each of 10 stages of the respiratory cycle, with the first stage being end-inspiration. We devised a 3-D semi-automated segmentation algorithm that segments the heart in the 4D-CT datasets acquired without contrast enhancement for use in estimating respiratory motion of the heart. Our semi-automated segmentation results were compared against interactive hand segmentations of the coronal slices by a cardiologist and a radiologist. The pairwise difference in segmentation among the algorithm and the physicians was on the average 11% and 10% of the total average segmented volume across the patient, with a couple of patients as outliers above the 95% agreement limit. The mean difference among the two physicians was 8% with an outlier above the 95% agreement limit. The 3-D segmentation was an order of magnitude faster than the Physicians' manual segmentation and represents significant reduction of Physicians' time. The segmented first stages of respiration were used in 12 degree-of-freedom (DOF) affine registration to estimate the motion at each subsequent stage of respiration. The registration results from the 32 patients indicate that the translation in the superior-inferior direction was the largest component motion, with a maximum of 10.7 mm, mean of 6.4 mm, and standard deviation of 2.2 mm. Translation in the anterior-posterior direction was the next largest component of motion, with a maximum of 4.0 mm, mean of 1.7 mm, and standard deviation of 1.0 mm. Rotation about the right-left axis was on average the largest component of rotation observed, with a maximum of 4.6 degrees, mean of 1.6 degrees, and standard deviation of 2.1 degrees. The other rotation and shear parameters were all close to zero on average indicting the motion could be reasonably well approximated by rigid-body motion. However, the product of the three scale factors averaged about 0.97 indicating the possibility of a small decrease in heart volume with expiration. The motion results were similar whether we used the Physician's segmentation or the 3-D algorithm.