Congenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin™, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 ± 0.11. Male-to-male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex. © 2004 Wiley-Liss, Inc.