We are interested in understanding how polarity is established in the early C. elegans embryo. nop-1(it142) was shown by Rose et al. (Dev. Biol.1995) to be a viable mutant that lacks a pseudocleavage furrow and has reduced cortical and central cytoplasmic flows. Since most of the partitioning (par) genes are required for cytoplasmic flows (R.J. Cheeks and B. Goldstein, in preparation), we wondered whether the reduced flows in nop-1 mutant embryos might be a sign that it142 is a hypomorphic allele of a gene in the par pathway. We examined the phenotype of nop-1(it142) embryos and found that a proportion of them had no cytoplasmic flows, and these embryos failed to hatch. Interestingly, most of these defective embryos either had a Par phenotype that resembled that produced by par-2 or par-5 loss of function, or failed to complete first cytokinesis. The penetrance of these two phenotypes was greatly enhanced (to 95%) in embryos in which nop-1 function was reduced by having it142 in trans to a deficiency. These results indicate that nop-1 plays an essential role in early embryonic events. Furthermore, we found that the Par phenotype of nop-1 mutant embryos was synergistically enhanced by either a homozygous mutation in par-4 or a heterozygous mutation in par-5. Disruption of par-1, par-3 or par-6 had no effect on the penetrance of this phenotype. Interestingly, the pseudocleavage defect of nop-1 embryos was suppressed by a homozygous mutation in par-5. Therefore, nop-1 genetically interacts with some components of the par pathway for the establishment of embryonic polarity. We set out to clone nop-1 as a step toward further defining its role in early embryogenesis. nop-1(it142) was previously mapped by Lesilee Rose on chromosome III, between dpy-17 and unc-32. Preliminary attempts identified cosmid B0336 as partially rescuing the weak flow phenotype of nop-1 embryos. However, this is likely to be due to a gain-of-function effect: using several mutations and deficiencies in the area, we refined the mapping of nop-1 and positioned it between sma-4 and kin-18, a region that excludes B0336. While this genetic region contains five genes with an early embryonic phenotype (Gonczy et al., Nature 2000), RNAi to these genes fails to phenocopy the Nop phenotype. We are currently refining the mapping of nop-1 using SNPs in the area, sequencing potential candidates and assaying for enhancement of the Nop phenotype by weak RNAi feeding; progress will be reported.