Family investigation is a reliable model to study the effects of both genetic and environmental factors on human health. This article studies kidney-yang deficiency syndrome and cold syndrome through family investigation and cDNA microarray technology, exploring the effects of both genetic and environmental factors on the health of family members. Particularly, these two syndromes were first assessed by the accumulated clinical scores measured by 40-item scoring tables among 15 family members. The family patterns were obtained and the correlation of these two syndromes was determined. Then the gene differential expression profiles among 12 family members were obtained using an 18,816 clones cDNA microarray. The profiles of the patients with typical kidney-yang deficiency syndrome and cold syndrome were compared to those of normal members and 89 differential expression genes were found. Further, only 22 genes were identified as known functions, and most (16 genes) were associated with the regulation of metabolism, temperature feeling, and growth. Therefore, the formation and development of these two syndromes have not only genetic but also environmental factors, including living conditions and lifestyle.