This is the first functional analysis in Drosophila of unfulfilled (unf; DHR51), the NR2E3 nuclear receptor superfamily ortholog of C. elegans fax-1 and human PNR. Both fax-1 and PNR mutations disrupt developmental events in a limited number of neurons, resulting in behavioral or sensory deficits. An analysis of two independent unf alleles revealed that unf mutants are characterized by one of two phenotypes. A proportion of the mutants eclosed but failed to expand their wings and were poorly coordinated. The remainder completed wing expansion but displayed severely compromised fertility. Consistent with the restricted neural expression of fax-1 and PNR, unf expression was detected in situ only in mushroom body neurons and a small number of other cells of the central nervous system (CNS). These data support the hypothesis that the wing expansion failure and the compromised fertility of unf mutants are the result of underlying neural defects.