Two blood samples containing autoagglutinins reactive in room temperature tests using low-ionic strength salt (LISS) reagents, but not by conventional saline-albumin or enzyme tests, are reported. The anti-P specificity of both sera, when tested near or diluted in group AB serum, was evident by their failure to agglutinate LISS-suspended Tj(a-),(p), and P1 red blood cells. However, one of the two samples displayed no anti-P specificity when diluted in LISS solution as opposed to group AB serum. Some urine samples inhibited this latter serum. Inhibition did not correlate with urinary Sda antigen content, nor with pH, Na+, K+, C1-, or osmolality levels. However, there was some correlation between inhibition and urinary conductivity levels. Moreover, partial inhibition was observed in tests with globoside. While there are no data to indicate that these LISS-dependent autoagglutinins are of clinical consequence in vivo, it is likely that they represent low-affinity autoantibodies reacting only in a low-ionic environment. They establish a further cause of anomalous serologic reactions associated with LISS techniques.