AbstractHeart determination is a gradual, cumulative process involving inductive and suppressive interactions between the heart mesoderm and nearby embryonic tissues. Our analysis of heart determination in the California newt,Taricha torosa, includes defect and otherin vivoexperiments, and explants in epidermal vesicles and into hanging drops.Explants of presumptive heart mesoderm from neurulae into hanging drops of a completely defined salt solution (Niu‐Twitty solution) produce beating hearts only infrequently. The addition of various other tissues and fractions of tissue homogenates changes the frequency and the rate of differentiation. These two parameters were used to assess the stimulatory and suppressive effects of tissues and tissue fractions on the differentiation of the presumptive heart mesoderm.At least three different factors are active in eliciting and regulating heart differentiation. A specific heart inductor in anterior endoderm increases the rate and the freqency of heart differentiation. A general stimulatory factor in epidermis and other embryonic tissues increases the frequency, but not the rate, of heart differentiation. An inhibitory agent in cranial fold and neural plate tissues delays or prevents heart differentiation. These three factors operate from intact tissues in the embryo or when explanted in vesicles or hanging drops, and are effectively present in a fraction (from sephadex column chromatography) of homogenates of the appropriate tissue