Rippling muscle disease is caused by mutations in the caveolin gene and in some cases is associated with autoimmune myasthenia. Limb girdle and distal patterns of weakness, exercise elicited muscle cramps, myalgias and stiffness have all been reported in association with the defining features of the rippling syndrome related to caveolin deficiency, i.e., wave like muscle contractions, percussion-induced rapid muscular contractions (PIRMC) and myoedema. To report on several members of a new autosomal dominant pedigree affected with rippling muscle disease that presented with exercise intolerance. Index case: A 43-year-old woman reported lack of endurance in physical activities since childhood. This limitation became particularly evident when running due to inability to keep up with her classmates. She found no difficulty with sustained, low level physical work or activities of daily living. CK was 460 IU. The physical examination revealed PIRMC, occasional, non-reproducible rippling of the calf muscles induced by manual compression and slight to moderate calf hypertrophy. Immediately after standing up, she had to walk on tiptoes. EMG was normal. Eight other examined family members, 13 to 46-year-old, reported exercise intolerance associated with increased CK (up to 13,000 IU in one case) but without noticeable weakness. Rippling was present in five and PIRMC in all of them. The muscle biopsy of several symptomatic patients showed slight, non-specific, myopathic signs. Immunohistochemistry revealed total absence of sarcolemic caveolin in both of the tested patients while dystrophin, sarcoglycans and dysferlin were preserved. Calpain was present on western blot testing. In the differential diagnosis of exercise intolerance clinicians should include rippling muscle disease and/or caveolinopathy along with substrate use defects and mitochondrial myopathies.