The purpose of this study was to evaluate the effects of a 13-week health-related fitness program on 10 Down syndrome subjects aged 8 to 18. An A-B-A time-series design was used, with data collected every 6 weeks for 43 weeks: The preintervention phase included four data collection points, and the intervention and postintervention phases included two data collection points each. Data obtained included resting heart rate, blood pressure, and results of a step test designed to measure cardiovascular fitness. Analyses of results revealed significant positive changes for resting heart rate (p < .0005), blood pressure (p < .01), and step test (p < .0001). Motivation and the type of program implemented were identified as particular reasons for positive outcomes. It was concluded that participation in regular physical activity may be beneficial for Down syndrome subjects, particularly because poor fitness levels have been closely associated with health risks such as cardiovascular disease.