Previous studies from our laboratory have revealed a complex set of genetic interactions involved in the control of pharyngeal development. One of the genes, lin-35, encodes a C. elegans Rb family member and functions as a transcriptional repressor. A second gene, ubc-18, encodes an E2 ubiquitin-conjugating enzyme and partners with the E3 ligase, ARI-1. A third gene, pha-1, encodes a novel cytoplasmic protein, which has previously been shown to play roles in pharyngeal development and embryogenesis. Double mutants in lin-35 and ubc-18 as well as lin-35 and certain alleles of pha-1 lead to defects in pharyngeal morphogenesis and concomitant larval arrest. Additionally, ubc-18; pha-1 double mutants show analogous synthetic defects. To address the molecular mechanism that underlies these genetic redundancies and to understand the developmental functions of these proteins, we have identified several suppressor mutations that alleviate the synthetic phenotypes of all three double mutant combinations. Two of the suppressors, sup-35 and sup-37, encode C2H2-type Zn-finger proteins, suggesting roles in transcriptional regulation. sup-35 is non-essential and is expressed broadly during embryogenesis. In contrast, sup-37 is required for viability, although expression is limited primarily to the pharynx. Multiple lines of genetic and molecular evidence indicate that SUP-35 and SUP-37 act as upstream negative regulators of PHA-1 activity. Our results also suggest that LIN-35 and UBC-18--ARI-1 function as negative regulators of SUP-35--SUP-37. Thus, in lin-35; ubc-18 double mutants, high levels of SUP-35--SUP-37 would lead to repression of pha-1 and resultant defects in pharyngeal development. Consistent with this model, over-expression of pha-1 in lin-35; ubc-18 strains suppresses double-mutant arrest. In addition, over-expression of SUP-35 in a wild-type background mimics pha-1 loss of function, and this phenocopy is dependent on the presence of wild-type sup-37, suggesting that SUP-35 may act upstream or in a complex with SUP-37. Additional findings further implicate a role for the C. elegans host cell factor ortholog, HCF-1, in the regulation of SUP-35--SUP-37 by LIN-35 and its co-partner EFL-1/E2F. Taken together, our data begins to piece together the components and regulatory networks underlying a complex series of genetic redundancies. Our findings also shed light on the control of organogenesis, including novel developmental roles for the LIN-35/Rb tumor suppressor.