A defect in mcb, encoding the cAMP-dependent protein kinase A (PKA) regulatory subunit in Neurospora crassa, which confers an apolar growth phenotype, is accompanied by an increase in PKA activity levels. Both PKA and CRE-1 [a key carbon catabolite repression (CCR) regulator] mediate the cellular response to carbon-source availability. Inactivation of the cre-1 gene resulted in reduced growth rate, abnormal hyphal morphology and altered CCR. Both PKA and CRE-1 affected morphology in a carbon-dependent manner, as fructose suppressed the apolar morphology of the mcb strain and enabled faster growth of the Deltacre-1 mutant. An increase in cre-1 transcript abundance was observed in mcb and a reduction in PKA activity levels was measured in Deltacre-1. CRE-1 is involved in determining PKA-dependent polarity, as an mcb;Deltacre-1 strain displayed partial reestablishment of hyphal polarity. Taken together, our results demonstrate regulatory interactions between PKA and CRE-1 that affect cell polarity in a filamentous fungus.