A case-control study was designed to test the association between joint hypermobility syndrome (JHS), an inherited disorder of collagen synthesis, and anxiety and phobic disorders. One hundred fourteen cases of JHS diagnosed at the rheumatology outpatient clinic of the Hospital del Mar (Barcelona) were compared to 59 control subjects randomly selected from patients seen at the same clinic. Both cases and controls were examined by a psychologist who used the Structured Clinical Interview for DSM-III-R and who was unaware of their medical diagnoses. DSM-III-R diagnoses of panic disorder, agoraphobia, and simple phobia, but not generalized anxiety disorder, dysthymic disorder, or major depression were found to be highly associated with JHS (age- and sex-adjusted odds ratio = 10.7). Mitral valve prolapse (MVP) was present only among JHS cases. Among cases of JHS, subjects with MVP were almost three times more likely to suffer from anxiety than subjects without MVP (odds ratio = 2.95), although the association was not statistically significant. The strong association between panic anxiety and JHS appears to occur at a higher level than the association between panic and MVP, and provides a new basis for further studies on the genetic background of panic-anxiety.