Tissue plasminogen activators (t-PAs) and derivatives thereof are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PAs and derivatives thereof via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PAs and derivatives thereof are also disclosed.