The tcplfit2 R package performs basic concentration-response curve fitting. The original tcplFit() function in the tcpl R package performed basic concentration-response curvefitting to 3 models. With tcplfit2, the core tcpl concentration-response functionality has been expanded to process diverse high-throughput screen (HTS) data generated at the US Environmental Protection Agency, including targeted ToxCast, high-throughput transcriptomics (HTTr) and high-throughput phenotypic profiling (HTPP). tcplfit2 can be used independently to support analysis for diverse chemical screening efforts.