We describe an attempt to measure effects of Mendelian phenotypes on human health (homeostasis) in man. We used the McKusick Catalogs as the source for descriptions of autosomal dominant, recessive, and X-linked phenotypes. Three hundred and fifty one entries (76% of the initial sample) were disadaptive causing an impairment, disability, or handicap. (Terms used are in accordance with World Health Organization (WHO) definitions.) Phenotypic effects were scored to measure impact on life-span, reproductive capability, and psychosocial characteristics. We found 1) 25% of the disadaptive Mendelian phenotypes were apparent at birth and over 90% by the end of puberty; age at onset is unimodal in distribution for autosomal recessive and X-linked diseases, and trimodal for autosomal dominant (with modes during morphogenesis, infancy, and early adult life); 2) 58% of phenotypes involved more than one anatomical or functional system; autosomal dominants were more likely to involve only a single system; 3) life-span was reduced in 57%, particularly in those with onset in pre- or intra-reproductive life, and more often in recessive and X-linked diseases (data corrected for genetic lethals); prognosis varied with system involvement; 4) reproductive capability was impaired in 69% of phenotypes; and 5) most phenotypes compatible with life beyond infancy caused psychosocial handicap and limited the access to schooling and work. These findings have implications for medical care.