Loss of variant histone H2A.Z in budding yeast cells leads to alterations in Sir protein-dependent transcriptional silencing, possibly due to impaired function of chromatin boundaries. We observed that deletion of HHO1, coding for linker histone H1, could suppress silencing defects seen in htz1Δ strains. We subsequently observed that loss of H1 also ameliorates the growth defects seen in strains lacking H2A.Z. HTZ1 is synthetically lethal with several dozen yeast genes; these genes have widely varying functions. To examine the specificity of the H1-H2A.Z interaction we examined whether loss of H1 can restore viability to synthetically lethal htz1Δ ykoΔ strains. Preliminary evidence suggests that loss of H1 specifically rescues the viability or slow growth of strains combining HTZ1 deletions with deletions of genes involved in histone deacetylation or ubiquitination. Finally, we have used chromatin immunoprecipitation to establish that strains lacking H2A.Z show reduced association of histone H1 with chromatin. Overall our experiments suggest that loss of H2A.Z triggers an H1-dependent disruption of normal chromatin structure.