We have studied the effects of mutations in a 6-base segment of Schizosaccharomyces pombe 7SL RNA, which lies within a 35-nucleotide domain whose sequence and secondary structure are conserved in RNAs from many divergent organisms, including the 7SL component of human signal recognition particle (SRP). Surprisingly, many changes in this region can be tolerated under normal growth conditions. An exception is the lethality of several mutations at positions 159 and 160, 2 nucleotides previously shown to be protected from RNase digestion by the 19-kDa canine SRP protein. Nucleotide 160 is, in addition, the most highly conserved base in a consensus sequence for the most common tetranucleotide loop in ribosomal RNAs. Mutations that are likely to affect the stability and/or conformation of the RNA give rise to a conditional phenotype: when osmolarity of the medium is raised, the RNAs become partially or completely defective in function at high temperature.