Ichthyoses are a heterogenous group of keratinization disorders, which are often associated with hypohidrosis. We report a 42-year-old man with generalized thick brownish scales and severe thermodysregulation leading to heat intolerance. Based on clinical, histological and genetic findings, autosomal recessive lamellar ichthyosis (ultrastructural electron microscopy type III) was diagnosed. Severe generalized hypohidrosis both at rest and after physical exercise (bicycle ergometer) was documented. Oral treatment with retinoids not only markedly improved the skin condition but also restarted the ability of the patient to thermoregulate by perspiration. The normalization of sweat-gland function was confirmed by gravimetrically measuring sweat rates before and after retinoid treatment. This report shows that retinoid therapy can markedly improve the quality of life in patients with generalized lamellar ichthyosis by reconstitution of perspiration.